Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance

  • Authors:
    • Feng-Ting Huang
    • Yong-Xun Zhuan-Sun
    • Yan-Yan Zhuang
    • Shu-Li Wei
    • Jian Tang
    • Wen-Bo Chen
    • Shi-Neng Zhang
  • View Affiliations

  • Published online on: August 22, 2012     https://doi.org/10.3892/ijo.2012.1597
  • Pages: 1707-1714
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Pancreatic cancer stem cells play a crucial role in tumorigenesis and chemoresistance. The Hedgehog signaling pathway is a key regulator in pancreatic tumorigenesis and drug resistance. To identify pancreatic cancer stem cells, tumorspheres derived from the PANC-1 pancreatic cancer cell line were cultured under a floating-culture system. PANC-1 tumorspheres possessed properties of self-renewal, differentiation, higher tumorigenesis and chemoresistance. It was observed that Hedgehog pathway is active in PANC-1 tumorspheres as shown by expression of hedgehog components Smo, Gil 1 and Gli 2, detected by quantitative RT-PCR and western blotting. After cyclopamine-mediated blockade of hedgehog, a decrease in proliferation of PANC-1 tumorspheres and G0/G1 transition were observed, as well as a decreased expression of Bmi-1 in PANC-1 tumorspheres. Cyclopamine reversed chemoresistance to gemcitabine, resulting in decreased expression of ABCG2 in PANC-1 tumorspheres. Taken together, our data indicate that PANC-1 tumorspheres have ‘stemness’ potential, and hedgehog signaling pathway plays an important role in the regulation of self-renewal and reversal of chemoresistance in cancer stem cells in pancreatic adenocarcinoma.
View Figures
View References

Related Articles

Journal Cover

November 2012
Volume 41 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Huang F, Zhuan-Sun Y, Zhuang Y, Wei S, Tang J, Chen W and Zhang S: Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance. Int J Oncol 41: 1707-1714, 2012
APA
Huang, F., Zhuan-Sun, Y., Zhuang, Y., Wei, S., Tang, J., Chen, W., & Zhang, S. (2012). Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance. International Journal of Oncology, 41, 1707-1714. https://doi.org/10.3892/ijo.2012.1597
MLA
Huang, F., Zhuan-Sun, Y., Zhuang, Y., Wei, S., Tang, J., Chen, W., Zhang, S."Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance". International Journal of Oncology 41.5 (2012): 1707-1714.
Chicago
Huang, F., Zhuan-Sun, Y., Zhuang, Y., Wei, S., Tang, J., Chen, W., Zhang, S."Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance". International Journal of Oncology 41, no. 5 (2012): 1707-1714. https://doi.org/10.3892/ijo.2012.1597